PLATELET REACTIONS UNDER CONTROLLED FLUID SHEAR STRESS

受控流体剪切应力下的血小板反应

• 批准号: 2292604
• 负责人: J. DAVID HELLUMS
• 金额: $ 0.89万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-07 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2292604
• 关键词: blood viscosity; mechanical stress; platelet activation; platelet aggregation

The overall goal of the research is to improve our understanding of reaction kinetics and mechanisms of platelet events of significance in cardiovascular disorders. We subject blood specimens to known, controlled levels of shear stress in a rotational viscometer and determine the response by use of the flow cytometric methods. These studies will be done both in the absence of added agents, and in the presence of platelet agonists and antagonists. Part of the work aims to improve and extend our flow cytometric methodology for studying platelet activation and aggregation in whole blood, and to analyze the results by means of a population balance mathematical model to determine the collision efficiency and breakage rate parameters as functions of biochemical environment, shear rate and shear exposure time. In parallel we will carry out studies using two thrombogenesis models developed by Dr. Ohshima and his colleagues at the University of Tsukuba. Both models use a fluorescent dye-light method of stimulation of thrombus formation, measure platelet thrombus initiation and growth rate, and allow quantitative assessment and control of fluid mechanical shear stress. One model incorporates a cultured endothelial cell monolayer in a cone- plate rotational viscometer. The viscometer applies a known, controlled shear stress to a platelet suspension in contact with the endothelial cell monolayer. A second model measures thrombus initiation and the rate of thrombus growth in blood vessels of rats by use of an intravital microscope-television system.

这项研究的总体目标是提高我们对 有意义的血小板事件的反应动力学和机制 心血管疾病。我们让血液样本接受已知的、可控的 旋转粘度计中的剪切应力水平，并确定 用流式细胞仪方法进行反应。这些研究将是 无论是在没有添加试剂的情况下，还是在存在血小板的情况下 激动剂和拮抗剂。部分工作旨在改进和扩展我们的 应用流式细胞术研究血小板活化和细胞因子 在全血中聚集，并通过A 确定碰撞的人口平衡数学模型 作为生化函数的效率和破碎率参数 环境、剪切速率和剪切曝光时间。同时，我们将 使用由Dr。 大岛和他在筑波大学的同事们。这两种型号都使用 一种刺激血栓形成的荧光染料光方法， 测量血小板血栓形成和生长率，并允许 流体机械剪应力的定量评价与控制。 一种模型将培养的内皮细胞单层合并在一个锥体中- 板式旋转粘度计。粘度计应用已知的、可控的 与内皮细胞接触的血小板悬浮液的剪切力 细胞单层。第二个模型测量血栓形成和血栓发生率。 大鼠血管内血栓生长的活体实验研究 显微镜-电视系统。